The goal of the South Carolina Clinical and Translational Research Institute (SCTR) is to create a sustainable home at the Medical University of South Carolina (MUSC) to advance clinical and translational research as a distinct discipline and facilitate collaboration across multiple disciplines. The overall approach focuses on: (1) implementing important advances in biomedical science to create opportunities for discovery, (2) removing barriers to facilitate the linkage of knowledge, experience and expertise across disciplinary boundaries, (3) providing training and mentoring experiences to enhance the pipeline for clinical and translational researchers with diverse training and backgrounds, and (4) fostering community engagement with a rapidly growing statewide population that is underserved by many systems to improve their participation and health outcomes. MUSC has long-standing experience leading successful clinical and translational research efforts that span the state. It is the leading state institution in extramurally funded research activities and has a rich research training portfolio. SCTR was established in 2007 with the vision that it would be the agent of change in transforming the research culture at MUSC and statewide via strong relationships with academic and community-based affiliates. Great progress has already been made including the development of an institutional K12 Career Development Program in Clinical and Translational Research, implementation of a pilot project program that funded 29 projects in the first two competitive rounds, and establishment of a robust collaboration with the NIH-funded CTSA at Vanderbilt University for assistance in the SCTR Biomedical Informatics Program. Joining the national CTSA Consortium will accelerate progress by further facilitating (1) development and interoperability of biomedical informatics systems, (2) active exchange of best processes and best practices in evidence-based medicine and community engagement, (3) advancement of clinical and translational science as a discipline and career path; and (4) shared knowledge, experience and collective influence in setting regional and national research agendas and health policy designed to generate the transformative results envisioned by the NIH Roadmap.